CMAAO Coronavirus Facts and Myth Buster: ICMR Vaccine : Dr KK Aggarwal

Participants: Dr KK Aggarwal, Dr Ashok Gupta, Dr AK Agarwal, Dr Ashok Gupta, Dr Suneela Garg, Dr DR Rai, Dr Narottam Puri, Dr JA Jayalal, Dr Jayakrishnan AV, Dr Alex Thomas, Dr Atul M Kochhar, Dr Glory Alexander, Ms Meenakshi Datta Ghosh, Mrs Upasana Arora, Dr K Kalra, Ms Ira Gupta, Dr S Sharma

Faculty: Dr NK Ganguly, Former Director-General, ICMR

Key points from the discussion

• A herd immunity of 60-70% is required to stop the spread of infection in the community; however, development of herd immunity will take time. This can be achieved with vaccine.
• A vaccine which gives 40% protection may not be ideal; if it gives 70% protection, it will stop transmission.
• In India, phase 1 and 2 trials only; phase 3 yet to be done. Nineteen of the vaccines around the world have completed phase 1, are in/completed phase 2 or have entered phase 3. Some international vaccines have entered phase 3, so may come out with a vaccine earlier than us.
• US FDA has brought out separate guidelines for animal toxicology studies for Covid vaccine.
• Different platforms are being used to make the vaccine safe. Very limited amount of the viral protein (such as preformed spike protein, receptor binding domain [RBD]) is used to make it as safe as possible. The whole cell vaccine (killed or attenuated) may cause problems as it contains all viral antigens, which might produce immune responses.
• Immune responses in humans differ. This is why three age groups will receive the vaccine: 18-55, 55-70, ≥70. Different concentrations are taken and multiple injections are needed – one to prime and the second to boost.
• The vaccine work will depend on whether neutralizing antibodies are formed. They are checked in two formats: live virus and ghost cells. Moderna vaccine (synthetic vaccine) was able to get neutralizing antibodies in 8 of its subjects and it also passed safety (there will be some swelling, redness at the site, fever, nausea but no serious adverse effects like cytokine storm, autoimmune reaction). Modernahas finished phase 2, but they have not published.
• Pfizer has taken four different constructs of mRNA vaccine with BioNTech. Two of them have completed phase 2.
• In India, Gennova Pharmaceuticals is developing MRNA vaccine and have almost finished preclinical studies. Their results in mice are good and in monkey challenge are excellent. They have completed studies on plasma and did not find any autoimmune reaction, cytokine storm or any deleterious immune reaction.
• Till phase 3 is done, there is no certainty that the vaccine will succeed. People may react differently according to the endemicity like the Rotavirus vaccine.
• No mRNA vaccine is in the market yet. Moderna and Pfizer vaccines have gone into human trials; Gennova are almost completing the animal and preclinical studies.
• Spike protein vaccine (AstraZeneca and Oxford vaccine):License has been given to several companies. In India, license has been given to Serum Institute of India. If the vaccine succeeds in phase 2, they will start manufacturing and release the vaccine as an emergency vaccine if phase 3 is successful.
• Novavax vaccine:Phase 2 is completed. It is entering phase 3 trials in Australia and Brazil. Matrigel adjuvant is used. It is funded by BARDA. Novavax has a joint venture with Cadila Pharma called CLP Biologicals in Ahmedabad.
• There is a global list of 19 prospective companies; no Indian company features on this list.
• The Johnson & Johnson vaccineis using Adeno-26 platform and pre-fusion spike protein, which has been successfully used by them in Ebola vaccine (RNA vaccine) and RSV vaccine. J&J has so far no agreement with any Indian company, but they are talking to Aurobindo, which has bought a small vaccine company from Pfizer in the US. It is using a vesicular stomatitis virus platform for vaccine development, which is likely to be manufactured in their unit in Hyderabad.
• Bharat Biotech vaccine: It is a whole cell killed vaccine. There are few challenges: If it has an alum adjuvant, then it might produce immune response. Since there are no human trials yet, we do not know how it will behave.
• Sinovac inactivated whole virus vaccinefrom China might be the first vaccine available. It is alum adjuvanted and is already in human trials. Formaldehyde is used to inactivate the virus.
• Most vaccine products are being tested in multiple countries.
• In India, the regulatory pathway to monkey studies is very long. For animal studies (monkey), one may have to go outside India (Gennova). There are very few BSL 3 facilities to do animal challenge studies.
• Many convalescent plasma have very little neutralizing antibodies. Some of them have almost no antibodies. The amount is not the same as it is produced in other infections.
• The amount of antibodies and the quality of antibodies which the vaccine will produce will be very critical.
• NK cells are markers of innate immunity. If NK cells are okay, then it is better.
• Mutations in the virus are happening rapidly now.
• Monoclonal therapy: One single antibody may not work, so a cocktail of three antibodies is preferred. Tocilizumab is actually IL-6 inhibitor.
• Safety of the vaccine was a cause for concern because of the nature of the virus right from Day 0. It attacks all organs through immunological response (cytokine storm). This is why manufacturers are trying to take as little as possible of the virus. Age difference is critical; hence, three groups of populations are being studied in trials. Like influenza vaccine, this vaccine may need to be taken every year.
• Cost of the vaccine will be a challenge.

Author : Dr KK Aggarwal, President CMAAO, HCFI and Past National President IMA

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